Pain, in particular chronic pain, can be a severely debilitating problem for many patients and it is often the case that the disease that is causing the pain itself becomes untreatable and the main focus of care is then altered to be palliative.
Even though the doctors and care providers best intentions are to provide optimum care for the patient, pain and symptom control can often not be as effective as hoped as the entire healthcare system has been designed to cure disease rather than alleviate pain and symptoms.
Effectively treating chronic pain poses a great challenge for doctors and health care providers as this type of pain often affects a patient's quality of life. A person's ability to carry out everyday tasks can be severely compromised due to chronic pain and as such the patient's personality can change.
For example when a patient is suffering from chronic pain caused by terminal cancer the only treatment option available is the relief of pain. Unfortunately up to 40% of cancer sufferers have unmet needs in pain suppression at the present time.
The caregiver's requirements are to provide the patient with a sufficient dose of medication to allow them to be freed as far as possible from their pain but there are inherent problems with this.
Often with the use of opiate related drugs the increased dosages of these drugs administered result in the patient becoming drowsy and unresponsive. Increased dosages of these medicaments can also cause respiratory failure and in consequence may result in premature death.
Physicians and nurses are often reluctant to give large doses of analgesic drugs, even to dying patients. Their fear is that the large doses provided will lead to sedation or respiratory depression. The result of this can be that the patient's pain is not adequately catered for.
In a position statement on treatment of pain at the end of life, the American Pain Society has recognised that terminal illness can often be accompanied by pain that is so severe that death can seem preferable. It has also been recognised that a substantial proportion of patients, particularly those in minority groups, are receiving inadequate analgesic treatment (Cleeland et al., 1994).
The American Pain Society has recommended that pain is made more visible and is therefore routinely charted as the fifth vital sign.
The use of cannabis as a medicine has long been known and during the 19th Century preparations of cannabis were recommended as a hypnotic sedative which were useful for the treatment of hysteria, delirium, epilepsy, nervous insomnia, migraine, pain and dysmenorrhoea.
Until recent times the administration of cannabis to a patient could only be achieved by preparation of cannabis by decoction in ethanol, which could then be swallowed or by the patient inhaling the vapours of cannabis by smoking the dried plant material. Recent methods have sought to find new ways to deliver cannabinoids to a patient including those which bypass the stomach and the associated first pass effect of the liver which can remove up to 90% of the active ingested dose and avoid the patient having to inhale unhealthy tars and associated carcinogens into their lungs.
Such dosage forms include administering the cannabinoids to the sublingual or buccal mucosae, inhalation of a cannabinoid vapour by vaporisation or nebulisation, enemas or solid dosage forms such as gels, capsules, tablets, pastilles and lozenges.
In 1988 a study was undertaken in order to determine the analgesic and anti-inflammatory activity of various cannabinoids and cannabinoid pre-cursors. Oral administration of CBD was found to be the most effective at inhibition of PBQ-induced writhing in mice. THC and CBN were found to be least effective at reducing analgesia and inflammation (Formukong et al., 1988).
Holdcroft et al. have shown that cannabinoids can have analgesic and possible anti-inflammatory properties. Administration of 50 mg of THC to a patient with Mediterranean fever resulted in a highly significant reduction in the amount of analgesia that the patient required (Holdcroft et al., 1997a).
A follow-on publication by the same authors examined the oral administration of oil of cannabis. The capsules containing 5.75% THC, 4.73% CBD and 2.42% CBN were administered to a patient with familial Mediterranean fever. During the 3 weeks of active treatment there was a decrease in the amount of escape medication (morphine) required by the patient (Holdcroft et al., 1997b). There were no changes in the measured inflammatory markers.
The use of different ratios of cannabinoids such as THC or CBD or their propyl variants, tetrahydrocannabinovarin (THCV) and cannabidivarin (CBDV), in the treatment of different diseases and conditions has previously been described in co-owned UK patent application GB2377633.
Specific ratios of THC and CBD or THCV and CBDV were reported to have been useful in the treatment or management of specific diseases or medical conditions. The following table details some of these areas.
Product GroupAreaRatio THC:CBDTarget TherapeuticHigh THC>95:5 Cancer pain;Migraine;Appetite stimulation.Even ratio50:50Multiple sclerosis;Spinal cord injury;Peripheral neuropathy;Neurogenic pain.Broad ratio CBD<25:75 Rheumatoid arthritis;inflammatory boweldisease.High CBD<5:95Psychotic disorders(schizophrenia);Epilepsy;Movement disorders;Stroke;Head injury;Disease modificationin rheumatoidarthritis and otherinflammatoryconditions;Appetite suppression.
A major disadvantage with the currently available drug therapies to treat severe chronic pain can be that the use of opioid based drugs may lead to unwanted side effects including constipation, sedation, pruritis, nausea and vomiting, respiratory depression, dysphoria and hallucinations and urinary retention.